5-HTP
5-Hydroxytryptophan
TL;DR
5-HTP is the direct precursor to serotonin, bypassing the rate-limiting step of tryptophan metabolism. Small trials support 150-300 mg/day for low mood and 100-300 mg at night for sleep onset, but it should never be combined with SSRIs or other serotonergic drugs.
Ideal For
- Adults with mild low mood who are not on serotonergic medication
- People with difficulty falling asleep rather than staying asleep
- Fibromyalgia patients seeking an adjunct for pain and stiffness
- Those with evening carbohydrate cravings
Avoid If
- You take SSRIs, SNRIs, MAOIs, triptans, tramadol or lithium
- You are pregnant or breastfeeding
- You have carcinoid syndrome or a serotonin-secreting tumour
- You have scleroderma or a history of eosinophilia-myalgia syndrome
- You are due for surgery involving serotonergic anaesthetic agents
Frequently Asked Questions
Overview
5-hydroxytryptophan sits one enzymatic step from serotonin. Tryptophan must first pass through tryptophan hydroxylase — the rate-limiting, feedback-controlled step — whereas 5-HTP crosses the blood-brain barrier without a transporter and is decarboxylated straight to serotonin. That directness is both its appeal and its main hazard.
The mood evidence is old and thin but not empty. A Cochrane review of 5-HTP and tryptophan found a signal of benefit over placebo across small trials, while noting poor methodological quality and the absence of modern comparisons against SSRIs. Sleep data are similarly modest: 5-HTP raises serotonin available for conversion to melatonin, and small studies show shortened sleep latency and increased slow-wave and REM sleep. There is a reasonable evidence base in fibromyalgia for pain and morning stiffness, and some appetite-suppression data at 300 mg before meals.
Two practical cautions matter. First, most peripheral 5-HTP is decarboxylated before reaching the brain, which drives the nausea that limits dosing; starting low and taking it with food helps. Second, combining 5-HTP with SSRIs, SNRIs, MAOIs, triptans or tramadol risks serotonin syndrome — this is a genuine contraindication, not a theoretical one.
How It Works
- Bypasses tryptophan hydroxylase, the rate-limiting step in serotonin synthesis
- Crosses the blood-brain barrier without competing for an amino acid transporter
- Decarboxylated by AADC to serotonin in both brain and periphery
- Increases substrate for nocturnal conversion of serotonin to melatonin
- Modulates descending pain inhibition, relevant to fibromyalgia and migraine
- Raises satiety signalling, reducing carbohydrate intake at higher doses
Quick Facts
- Direct precursor to serotonin
- Supports mood and emotional well-being
- May improve sleep quality
- Can help reduce appetite and cravings
- Crosses blood-brain barrier easily
Benefits & Outcomes
Serotonin Support
5-HTP raises serotonin synthesis but carries real interaction risk and thin outcome evidence.
Depression Symptom Reduction
5-HTP shows promise in small trials but lacks the rigorous evidence base of saffron or St John's Wort.
Sleep Maintenance
5-HTP has weak sleep evidence and meaningful interaction risk.
Melatonin Production
5-HTP is the direct serotonin precursor; since melatonin is synthesized from serotonin, it supplies the substrate for pineal production, with sleep-onset evidence in trials.
Mood Stabilization
Early trials suggested 5-HTP was comparable to some antidepressants, but the evidence base is old, small and methodologically weak.
Improved Sleep Quality
5-HTP is widely sold as a sleep aid but human trial evidence is thin and mostly from small studies combining it with GABA.
Stress Resilience
There is no meaningful trial evidence that 5-HTP improves stress resilience.
Supporting Research7 studies
Tryptophan and 5-hydroxytryptophan for depression
Shaw K, Turner J, Del Mar C
Only 2 of 108 identified trials met quality criteria: 5-HTP outperformed placebo on depressive symptoms, but across just 64 patients.
5-Hydroxytryptophan for depression: a systematic review of clinical trials
Shaw K, Turner J, Del Mar C
Only two of 108 identified trials were of adequate quality; the evidence was too weak to recommend routine use
Satiety and amino-acid profile in overweight women after a new treatment using a natural plant extract sublingual spray formulation
Rondanelli M, Klersy C, Iadarola P +2 more
To test the effect on satiety of a formulation comprising plant extracts naturally containing 5-hydroxytryptophan
Serotonin a la carte: supplementation with the serotonin precursor 5-hydroxytryptophan
Turner EH, Loftis JM, Blackwell AD
5-HTP raises CNS serotonin readily, but the clinical trial base is small and dated, and peripheral serotonin exposure raises valvulopathy and drug-interaction concerns.
Double-blind study of 5-hydroxytryptophan versus placebo in the treatment of primary fibromyalgia syndrome
Caruso I, Sarzi Puttini P, Cazzola M +1 more
5-HTP 100 mg three times daily improved tender points, pain, sleep and fatigue versus placebo over 30 days in primary fibromyalgia.
An eosinophilia-myalgia syndrome related disorder associated with exposure to L-5-hydroxytryptophan
Michelson D, Page SW, Casey R +7 more
Contaminant peaks analogous to those implicated in tryptophan-associated eosinophilia-myalgia syndrome were found in the 5-HTP product consumed by affected family members.
Primary fibromyalgia syndrome and 5-hydroxy-L-tryptophan: a 90-day open study
Sarzi Puttini P, Caruso I
Open-label 90-day treatment improved fibromyalgia symptoms from baseline, but with no placebo arm the placebo response cannot be separated out.
Safety Information
Potential Side Effects
Generally safe but should not be combined with antidepressants without medical supervision. May cause nausea initially. Start with low dose.
Contraindications
Concurrent serotonergic medication, pregnancy and lactation, carcinoid syndrome, and scleroderma. Use caution in anyone with a history of eosinophilia-myalgia syndrome linked to contaminated tryptophan products.
Drug Interactions
- SSRIs and SNRIs — serotonin syndrome risk, do not combine
- MAOIs — severe serotonin syndrome risk
- Triptans and tramadol — additive serotonergic effect
- Carbidopa — raises central 5-HTP levels and has caused scleroderma-like reactions
- Sedatives — additive drowsiness
Pregnancy & Breastfeeding
Pregnancy: insufficient_data
Breastfeeding: insufficient_data
Dosage Guidelines
Dosage Used in Studies
50-300 mg
Best Time to Take
Divided doses with meals for mood; single evening dose for sleep
Best Form
Time-release Griffonia-derived 5-HTP for overnight use; immediate-release for daytime dosing
Bioavailability
Roughly 70% orally bioavailable and does not require an active transporter to enter the brain, though much is decarboxylated peripherally before it gets there.
Forms Compared
Griffonia simplicifolia extract
Immediate-release capsules
Time-release tablets
With EGCG or carbidopa (clinical only)
Food & Timing
With food to reduce nausea; sleep doses 30-45 minutes before bed
Medical Disclaimer
The information provided on this website is for educational and informational purposes only and is not intended as a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition or before starting any supplement regimen.
Individual results may vary. The statements on this website have not been evaluated by the Food and Drug Administration. Products and information are not intended to diagnose, treat, cure, or prevent any disease.